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Chimeric Molecules (chimeric + molecule)

Distribution by Scientific Domains

Life Sciences	60%

Selected Abstracts

Possible role of Hes5 for the rostrocaudal polarity formation of the tectum

DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 3 2004
Jun Kimura
The alar plate of the mesencephalon differentiates into the optic tectum. Retinal fibers project to the tectum topographically in a retinotopic manner. Engrailed (En) is responsible for the tectum polarity formation and regionalization. Former study indicated the presence of the molecule whose expression is repressed by En and that represses the isthmus-related gene expression. To isolate such molecules, we constructed a subtracted library between cDNA population of the normal rostral mesencephalon and of the rostral mesencephalon that misexpresses En2. From the library, we isolated cHes5, a chicken homolog of Drosophila hairy/Enhancer of split. cHes5 begins to be expressed in the rostral part of the E2 mesencephalon, and spreads to caudal mesencephalon by E3. To our expectation, cHes5 expression was repressed by En2. Furthermore, misexpression of cHes5 in the mesencephalon inhibited expression of ephrinA2, a marker of caudal mesencephalon. An active repressor form of Hes5, which is a chimeric molecule of Hes5 and repressor domain of En2, showed a similar but more severe phenotype. The results indicate that Hes5 is regulated by En and is responsible for rostral identity of mesencephalon by repressing ephrinA2. [source]

Neuroprotective effect of interleukin-6 and IL6/IL6R chimera in the quinolinic acid rat model of Huntington's syndrome

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001
Jean-Charles Bensadoun
Abstract Ciliary neurotrophic factor prevents behavioural deficits and striatal degeneration in rat and primate models of Huntington's disease. Interleukin-6, another member of the cytokine family, and the chimeric molecule (IL6/IL6R) in which interleukin-6 and its soluble receptor are fused, have been shown to exert trophic action on various neuronal populations in the central nervous system. Therefore, we investigated the neuroprotective effect of these two molecules in the quinolinic acid model of Huntington's disease. LacZ-, interleukin-6- and IL6/IL6R-expressing lentiviral vectors were stereotaxically injected into the striatum of Wistar rats. Three weeks later the animals were lesioned through the intrastriatal injection of 180 nmol of quinolinic acid. The extent of the striatal damage was significantly diminished in the rats that had been treated with interleukin-6 or IL6/IL6R. The neuroprotective effect was, however, more pronounced with the IL6/IL6R chimera than with interleukin-6 as indicated by the volume of the lesions (38.6 ± 10% in the IL6/IL6R group, 63.3 ± 3.6% in the IL-6 group and 84.3 ± 2.9% in the control group). Quantitative analysis of striatal interneurons further demonstrated that the IL6/IL6R chimera is more neuroprotective than IL-6 on ChAT- and NADPH-d-immunoreactive neurons. These results suggest that the IL6/IL6R chimera is a potential treatment for Huntington's disease. [source]

Molecular determinants of hyperosmotically activated NKCC1-mediated K+/K+ exchange

THE JOURNAL OF PHYSIOLOGY, Issue 18 2010
Kenneth B. Gagnon
Na+,K+,2Cl, cotransport (NKCC) mediates the movement of two Cl, ions for one Na+ and one K+ ion. Under isosmotic conditions or with activation of the kinases SPAK/WNK4, the NKCC1-mediated Cl, uptake in Xenopus laevis oocytes, as measured using 36Cl, is twice the value of K+ uptake, as determined using 86Rb. Under hyperosmotic conditions, there is a significant activation of the bumetanide-sensitive K+ uptake with only a minimal increase in bumetanide-sensitive Cl, uptake. This suggests that when stimulated by hypertonicity, the cotransporter mediates K+/K+ and Cl,/Cl, exchange. Although significant stimulation of K+/K+ exchange was observed with NKCC1, a significantly smaller hyperosmotic stimulatory effect was observed with NKCC2. In order to identify the molecular determinant(s) of this NKCC1-specific activation, we created chimeras of the mouse NKCC1 and the rat NKCC2. Swapping the regulatory amino termini of the cotransporters neither conferred activation to NKCC2 nor prevented activation of NKCC1. Using unique restrictions sites, we created additional chimeric molecules and determined that the first intracellular loop between membrane-spanning domains one and two and the second extracellular loop between membrane-spanning domains three and four of NKCC1 are necessary components of the hyperosmotic stimulation of K+/K+ exchange. [source]

Thymus-leukemia antigen (TL) as a major histocompatibility complex (MHC) class Ib molecule and tumor-specific antigen

CANCER SCIENCE, Issue 6 2004
Kunio Tsujimura
Mouse thymus-leukemia antigens (TL) belong to the family of major histocompatibility complex (MHC) class Ib antigens and have a unique mode of expression, i.e., in contrast to other MHC class Ib or la antigens, they are found restricted to the intestines in all mouse strains, but also in the thymus of certain strains (TL+ strains). Nevertheless, a proportion of T lymphomas/leukemias in strains that do not express TL in the thymus (TL, strains) feature TL as a tumor antigen. TL was originally defined serologically, but subsequently we have succeeded in generating T cell receptor (TCR) ,, and ,, cytotoxic T lymphocytes (CTL) recognizing TL. By use of TL tetramers free from peptides and transfectants expressing various TL/H-2 chimeric molecules, we have been able to show that TL-specific CTL recognize the ,1 /,2 domain of TL without any additional antigen molecules. We previously reported that one of TL's functions in the thymus is positive selection of TCR,, CTL. Recent studies with TL tetramers revealed that they can bind to normal intestinal intraepithelial lymphocytes (ilEL) and thymocytes in a CD8-dependent, but TCR/CD3-independent manner, while their binding to TL-specific CTL is TCR/CD3-and CDS-dependent. The possible significance of these findings in relation to the roles of TL in the intestines is discussed. We have long been interested in TL as a model tumor antigen which shares characteristics with human differentiation tumor antigens, and we have demonstrated that growth of TL+ lymphoma cells in vivo is suppressed by immunization with TL+ skin or dendritic cells (DC) from TL transgenic mice. In addition, anti-tumor effects against TL+ T lymphomas were obtained by adoptive transfer of TL tetramer strongly-positive TL-specific CTLs. [source]

Activity and Stability of Hammerhead Ribozymes Containing 2,- C- Methyluridine: a New RNA Mimic

CHEMISTRY & BIODIVERSITY, Issue 2 2005
Mariana Gallo
We propose 2,- C -methylnucleotides as a new class of 2,-modified RNA mimics. These analogues are expected to provide 2,-OH groups capable of reproducing the interactions observed in natural RNA and, due to the presence of the Me group, to possess increased stability towards nucleases. In this work, we investigate the catalytic activity and nuclease resistance of hammerhead ribozymes carrying 2,- C -methyluridines in positions 4 and 7 of the catalytic core. We describe the in vitro activity of these chimeric molecules and their stability in cell lysate, fetal calf serum, and cell culture medium. The data show that, when only position 4 is modified, activity decreases twofold; while, when both 4 and 7 positions are substituted, a sevenfold drop in activity is observed. Regarding biological stability, the main increase of the half-life time is observed when position 7 is modified. These results suggest that 2,- C -methylnucleotides may be useful in the design of chemically synthesized RNA mimics with biological activity. [source]